It is normal practice with moisture sensitive pharmaceutical materials intended for parenteral use to package such materials in a glass vial with a rubber stopper to minimise moisture ingress and maintain product stability. Plastics material vials are sometimes required for a product where the high pH of the reconstituted solution may attack glass, but in general they are to be avoided because even the best are permeable to water vapour to some extent, and result in a shorter shelf life. Although careful control of the manufacturing and processing conditions may reduce the product moisture content to acceptable levels, there are times when this will not be sufficient, and some form of desiccation would be required. While this is fairly straightforward for oral dosage forms by the inclusion of desiccants in the pack, etc. the demands for sterility in a parenteral product mean that this approach cannot be used.
An example of a moisture sensitive pharmaceutical substance is a pharmaceutically acceptable derivative of the .beta.-lactamase inhibitor clavulanic acid, such as potassium clavulanate. Potassium clavulanate is both hygroscopic and readily hydrolysed by water, so for handling and long term storage of potassium clavulanate it is necessary for the immediate environment to be kept dry, e.g. 30% Relative Humidity ("RH") or less, preferably 10% RH or less.
Potassium clavulanate is a .beta.-lactamase inhibitor, and is often provided in a formulation in combination with a partner .beta.-lactam antibiotic. A partner which is often used in injectable formulations is amoxycillin in the form of sodium amoxycillin. Sodium amoxycillin is often used in such formulations in the form of spray-dried sodium amoxycillin, which is a powerful desiccant, and when contained together with potassium clavulanate in a sealed vial such forms of sodium amoxycillin can exert a dehydrating effect which helps to preserve the potassium clavulanate. Other forms of sodium amoxycillin, such as the anhydrous crystalline form disclosed in EP 0131147 are less desiccating, and although it would be desirable to use such forms in formulations together with potassium clavulanate because of the inherent greater purity of the crystalline form, the problem arises that these forms can be insufficiently desiccating to protect the potassium clavulanate.
Packaging systems are known which can desiccate tablets and capsules for swallowing by a patient. For example FR 2660634A discloses a blister pack for tablets in which two blisters are arranged side by side with an interconnecting channel. One of the blisters contains the tablet and the other a desiccant material to desiccate the tablet. EP 0466068A discloses a similar arrangement in which a capsule is desiccated.
It is an object of this invention to provide a desiccating package which inter alia is suitable for use with moisture sensitive pharmaceutical substances and allows sterile dissolution for parenteral administration without the problem of contamination by desiccant. Other objects and advantages of the invention will be apparent from the following description.